The proposed experimental work is to investigate the mechanisms of chromosomal replication. Efforts will be directed at defining the DNA synthsis which remains in an in vitro system after ultraviolet irradiation. This synthesis is independent of replication but requires ATP. We find certain repair-deficient mutants are not able to continue this synthesis, suggesting that we may be able to define the role of a repair function. We also plan to continue our studies into the mechanism of the anti-tumor agent Bleomycin. This drug has been shown to nick DNA. Our studies in vitro indicate that it does not interfere directly with replicative DNA synthesis, but does elicit a repair reaction. The relationship of this process to an overall inhibition of replication will be pursued.